Tuesday, April 21, 2015

Hygiene Hypothesis: Explaining the Increase in Autoimmune Disorders

Modern medicine has proved miraculous in its ability to prevent disease and increase the average life expectancy. However, the decrease in preventable disease has been correlated to an increase in autoimmune disorders. The most probable mechanism for explaining this trend is the hygiene hypothesis. The hygiene hypothesis stipulates that increased standard of living, meaning better hygiene and modern medicine, leads to a decreased exposure to microorganisms which in turn causes autoimmune disorders from diminished natural tolerance. Published online by the Cold Spring Harbor Laboratory Press, a study by Bach and Chatenoud provides evidence to corroborate the hygiene hypothesis via incidence of diabetes in mice living in varied sanitation conditions. The purpose of the experiment was to understand the protective mechanisms underlying infectious disease and thereby deduce a potential therapy for preventing autoimmune disorders.

Insulin dependent diabetes (or type 1 diabetes) is an autoimmune disease where the pancreas does not produce insulin as a result of an immune response directed at the pancreas. Type 1 diabetes is found through out the world, but is most prevalent in northern Europe and Americas. There are progressively less cases as one travels south (Figure 1). The statistical decline in diabetes as one gets closer to the equator is juxtaposed with the increase in infectious diseases (Figure 2). The fact that Figure 1 and Figure 2 are basically mirror images of each other is partly justified by genetics. Genetics explains how isolated populations have increased incidence of diabetes; however, with globalization genetic differences are relatively diminutive in nature. Particularly shown by increased type 1 diabetes rates for first generation migrants from countries of low rates to countries with high rates (Bodansky et al. 1992).

Figure 1. Frequency of Type 1 diabetes worldwide. Incidence of type 1 diabetes in children 0 - 14 yr. The data used in map creation are from www.eatlas.idf.org

Figure 2. Incidence of childhood diarrheal diseases (the data used in map creation are from www.cdc.gov)

The higher the standard of living, the better the medical care and sanitation conditions. When medical care is superior it is less likely for people to get sick or if they do, they are less likely to remain sick. Additionally, developed countries have better sanitation, as in people are cleaner. On the whole, the consequence is a decrease in exposure to microbes at a young age. The study by Bach and Chatenoud looked a non-obese diabetic (NOD) mice and exposure to varied hygiene conditions. Incidence of diabetes in the mice, when other environmental factors were controlled, was highest when sanitation conditions were best. As opposed to when sanitation conditions are worse and the frequency of disease decreased. The effects of increased sanitation could be reverse by raising newborns of Caesarean delivery, in unsanitary conditions. Diabetes was completely prevented in mice raised in a clean environment, which were purposefully exposed to an infectious microorganism.

Natural immune tolerance is an organism’s ability to recognize, and thereby not attack, its own proteins or antigens. In autoimmune diseases, the body’s natural tolerance malfunctions so that an immune response is generated against itself. The results can be debilitating and catastrophic for the ability of the body to function correctly. The basis of the hygiene hypothesis is the protective role played by infectious agent in preventing autoimmune disorders. A study by Calcinaro et al., found that NOD mice exhibited lower frequencies of diabetes by using lactobacillus derived from the gut. Some how the body reacting to bacteria from the gut prevents the body from attacking the pancreas to cause diabetes. Bach hypothesized that those immune responses from infectious agents, which are intensive and involve a variety of pathways “compete for consumption of homeostatic factors” with weaker immune responses, such as those from the body’s own cells (2002). The immune system is primed for action against antigens, which has a greater affinity for infectious disease, but in the absence of disease the body can react to antigens from its own cells. Bystander suppression may also be at play, where immunological activity can down regulate close range immune responses by causing regulator molecule for suppression to elongate their live span (Kimball, 2013). Other mechanisms, such as toll-like receptor agonists, may also play a role in the development of autoimmune disorders.

The hygiene hypothesis is logical, but with little experimental evidence to provide supporting proof. Part of the problem lies in the breadth of variables associated with immune system, autoimmune disorders, and antigens. The immune system is astoundingly complex while autoimmune disorders and antigens are innumerous. Thus, to definitively prove the hygiene hypothesis would be a major undertaking requiring considerable effort, time, and money. However, this does not mean potential applications for treatment of autoimmune diseases are not possible. The most likely therapy revolves around development of chemical extracts to illicit an innocuous immune response at a young age. Yet, FDA regulations would probably prevent administering an extract from an infectious disease to a child for the purpose of producing an immune response in an effort to prevent autoimmune disorders. All in all, the hygiene hypothesis is a very likely explanation for the rise of autoimmune disorder and provides a basis for understanding said autoimmune disorders in hopes of stemming the increase

6 comments:

I think that this is an interesting article! It made me think about going to the doctor, and how much hand sanitizer is used by people in health care offices--it's kind of ironic, that something that is so important for the doctors could use may have the potential to inflict such serious conditions. Despite the high level of cost and difficulty of obtaining data from thorough research, it may be merited. The information that is collected could have the potential to be important in discovering breakthroughs in research of the prevalent issue of autoimmune disorders. It will be interesting to see if/when in the future this hypothesis continues to be speculated, and whether or not there will ultimately be research done.

While the hygiene hypothesis is definitely interesting, I don't think it could ever be considered a definitive answer to why people get autoimmune disorders. Since records of autoimmune disorders like diabetes have been around for a long time, the hygiene hypothesis doesn't really help explain why the immune system attacks the body in the first place. It is also important to look think critically about world maps that claim to show a relationship between two variables because of the infinite number of confounding variables that are involved. People in living in the same areas of the world have a lot in common with each other, so it is important to look at the map and think about the things like diet, access to health care, and environment that may play a role as well.

I found the studies conducted on mice quite interesting because they may begin to offer causational information on microbial exposure rather than the simply correlational information on hygiene and immune diseases in humans. I wonder if exposure to microbes is most important early in life, when the immune system is still critically developing.

This was a really intriguing post! Toward the end you mentioned that you did not think the FDA would likely not allow the administration of an extract from an infectious disease to children, yet isn't that essentially the basis of vaccinations? I don't think that option should be ruled out yet!

I never heard of hygiene hypothesis so I found it very interesting to learn about it. I think more experiments should be done before any major conclusions can be made. I will definitely look more into this idea.